Colorectal Cancer News

Scientists Developing New DNA Tests for Colon Cancer

A new generation of DNA tests for colon cancer seems likely to improve the detection both of cancers and of the precancerous polyps that precede them. The tests could detect tumors at an early stage, including those not picked up by a colonoscopy.

Colon tumors shed blood and cells that are detectable in the stool. Tests for blood have reduced deaths from colorectal cancer only slightly, because they are not very sensitive to precancerous polyps, the stage at which cancer is best prevented.

Dr. Bert Vogelstein of Johns Hopkins University discovered the series of mutations by which a colon polyp advances to full cancer, leading researchers to measure mutations in DNA. But no single mutation predicts a patient’s risk, and the mutation tests, though more accurate than the blood tests, have not been a decisive improvement.

A new generation of tests being developed depends on a different process in cancer cells. All cells switch off the genes they do not need by attaching small chemicals called methyl groups to certain sites along their DNA. In cancer cells, there is generally less methylation than usual, except for certain regions of DNA where the methylation process is taken to excess, perhaps because the cells need to shut down tumor suppressor genes. These and other genes are highly methylated in colon tumors and other kinds of cancer.

Madison, WI based Exact Sciences is developing a colon cancer test based on highly methylated DNA. Last month, researchers reported that by testing for methylated DNA, they could detect colon tumors and polyps, distinguishing them from normal tissue with 100 percent sensitivity and with no false positives.

The tests were performed directly on tumors and are expected to be less accurate in the real world, in which they would have to work in stool samples. Most of the DNA in stool is from bacteria, and the methylated DNA is a fraction of the 0.01 percent that is human DNA.

Kevin T. Conroy, chief executive of Exact Sciences, said he expected that the test, when applied to stool samples, would detect at least half of all precancerous polyps and 85 percent of actual cancers. Results of a trial now under way in 1,600 patients will be reported in October, he said.

The test would cost less than $300, and samples could be collected at home. Patients would be advised to take the test every three years. People with a positive result would then have a colonoscopy to verify and remove any polyps, with the result that colonoscopies could be focused on high-risk patients instead of the population at large.